CN101578275A - 苯胺基哌嗪衍生物及其使用方法 - Google Patents
苯胺基哌嗪衍生物及其使用方法 Download PDFInfo
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- CN101578275A CN101578275A CNA2007800490776A CN200780049077A CN101578275A CN 101578275 A CN101578275 A CN 101578275A CN A2007800490776 A CNA2007800490776 A CN A2007800490776A CN 200780049077 A CN200780049077 A CN 200780049077A CN 101578275 A CN101578275 A CN 101578275A
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- alkylidene group
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- cancer
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- 238000000034 method Methods 0.000 title claims abstract description 302
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- -1 heterocyclic radical Chemical class 0.000 claims description 177
- 125000000217 alkyl group Chemical group 0.000 claims description 104
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- 150000003839 salts Chemical class 0.000 claims description 58
- 229910052799 carbon Inorganic materials 0.000 claims description 53
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Classifications
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- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU747705C (en) | 1997-12-13 | 2004-09-23 | Bristol-Myers Squibb Company | Use of pyrazolo (3,4-b) pyridine as cyclin dependent kinase inhibitors |
US6413974B1 (en) | 1998-02-26 | 2002-07-02 | Aventis Pharmaceuticals Inc. | 6,9,-disubstituted 2-[trans-(4-aminocyclohexyl) amino] purines |
WO2000062778A1 (en) | 1999-04-15 | 2000-10-26 | Bristol-Myers Squibb Co. | Cyclic protein tyrosine kinase inhibitors |
PL365170A1 (en) | 2000-07-26 | 2004-12-27 | Bristol-Myers Squibb Company | N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl] carboxamide inhibitors of cyclin dependent kinases |
CA2422376A1 (en) | 2000-09-15 | 2002-03-21 | Vertex Pharmaceuticals Incorporated | Isoxazoles and their use as inhibitors of erk |
US6818663B2 (en) | 2002-05-17 | 2004-11-16 | Hoffmann-La Roches | Diaminothiazoles |
DE10250110A1 (de) * | 2002-10-28 | 2004-05-13 | Bayer Cropscience Ag | Thiazol-(bi)cycloalkyl-carboxanilide |
FR2856685B1 (fr) * | 2003-06-25 | 2005-09-23 | Merck Sante Sas | Derives de thiazolylpiperidine, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent |
AU2006209183B2 (en) | 2005-01-26 | 2009-11-19 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
CA2649043C (en) | 2006-04-19 | 2013-09-17 | Astellas Pharma Inc. | Azolecarboxamide derivative |
WO2008054749A1 (en) * | 2006-10-31 | 2008-05-08 | Schering Corporation | 2-aminothiazole-4-carboxylic amides as protein kinase inhibitors |
WO2008106692A1 (en) | 2007-03-01 | 2008-09-04 | Novartis Vaccines And Diagnostics, Inc. | Pim kinase inhibitors and methods of their use |
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- 2007-10-29 CN CNA2007800490776A patent/CN101578275A/zh active Pending
- 2007-10-29 CA CA2668210A patent/CA2668210C/en not_active Expired - Fee Related
- 2007-10-29 AU AU2007314342A patent/AU2007314342B2/en not_active Ceased
- 2007-10-29 EP EP07853013.6A patent/EP2078003B1/de active Active
- 2007-10-29 JP JP2009534691A patent/JP5063700B2/ja not_active Expired - Fee Related
- 2007-10-29 MX MX2009004786A patent/MX2009004786A/es not_active Application Discontinuation
- 2007-10-29 WO PCT/US2007/022829 patent/WO2008054702A1/en active Application Filing
- 2007-10-29 US US12/447,712 patent/US9206142B2/en active Active
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- 2007-10-30 AR ARP070104809A patent/AR063721A1/es not_active Application Discontinuation
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CN102603667A (zh) * | 2012-02-10 | 2012-07-25 | 合肥工业大学 | 一种n-(2-氯-6-甲基苯基)-2-(苯丙烯酰胺)噻唑-5-甲酰胺衍生物、其制备方法及其用途 |
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CN102993124A (zh) * | 2012-11-25 | 2013-03-27 | 大理学院 | 取代哌嗪类化合物及其制备方法和药物用途 |
WO2014194667A1 (zh) * | 2013-06-05 | 2014-12-11 | 中国科学院上海药物研究所 | 一类炔基杂环类化合物及其应用 |
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CN105555785A (zh) * | 2013-06-18 | 2016-05-04 | 4Sc新发现股份有限公司 | 作为dyrk激酶抑制剂的2,3-二氢苯并呋喃-5-基化合物 |
CN105829293A (zh) * | 2013-12-20 | 2016-08-03 | 中国人民解放军军事医学科学院毒物药物研究所 | 新型哌啶氨甲酰类化合物、制备方法及其用途 |
US9840489B2 (en) | 2013-12-20 | 2017-12-12 | Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. China | Piperidine carboxamide compound, preparation method, and usage thereof |
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US11447463B2 (en) | 2013-12-20 | 2022-09-20 | Institute of Pharmacology and Toxicology Academy of Millitary Medical Sciences P.L.A. China | Piperidine carboxamide compound, preparation method, and use thereof |
CN113620863A (zh) * | 2015-09-14 | 2021-11-09 | 内盖夫国家生物技术研究所 | 新的哌嗪和哌啶衍生物、它们的合成及其用途 |
CN113620863B (zh) * | 2015-09-14 | 2024-04-05 | 内盖夫国家生物技术研究所 | 新的哌嗪和哌啶衍生物、它们的合成及其用途 |
CN112204017A (zh) * | 2018-04-27 | 2021-01-08 | 国立大学法人大阪大学 | 苯并异噁唑化合物 |
CN112204017B (zh) * | 2018-04-27 | 2024-08-20 | 国立大学法人大阪大学 | 苯并异噁唑化合物 |
CN115590854A (zh) * | 2019-12-25 | 2023-01-13 | 安斯泰来制药株式会社(Jp) | 哒嗪基噻唑甲酰胺类化合物 |
CN115626919A (zh) * | 2019-12-25 | 2023-01-20 | 安斯泰来制药株式会社 | 哒嗪基噻唑甲酰胺类化合物 |
CN115590854B (zh) * | 2019-12-25 | 2024-06-07 | 安斯泰来制药株式会社 | 哒嗪基噻唑甲酰胺类化合物 |
Also Published As
Publication number | Publication date |
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AU2007314342A1 (en) | 2008-05-08 |
TW200829583A (en) | 2008-07-16 |
WO2008054702A1 (en) | 2008-05-08 |
KR20090075873A (ko) | 2009-07-09 |
JP2010508274A (ja) | 2010-03-18 |
EP2078003A1 (de) | 2009-07-15 |
EP2078003B1 (de) | 2017-03-08 |
AR063721A1 (es) | 2009-02-11 |
CA2668210C (en) | 2013-03-12 |
MX2009004786A (es) | 2009-06-05 |
US20120328691A1 (en) | 2012-12-27 |
AU2007314342B2 (en) | 2013-02-21 |
CA2668210A1 (en) | 2008-05-08 |
IL198397A0 (en) | 2010-02-17 |
US9206142B2 (en) | 2015-12-08 |
JP5063700B2 (ja) | 2012-10-31 |
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